# Beyond Reserve: Dynamic Neurocognitive Adaptation

> **NIH NIH P20** · CLEVELAND CLINIC FOUNDATION · 2024 · $173,500

## Abstract

Our proposed project focuses on understanding the concepts of reserve and resilience, switching from a static 
perspective often applied in the literature to dynamic adaptation to the environment. Our validated dynamic 
Neurocognitive Adaptation (dNA) Scale will explore how individuals are engaged in protective cognitive and 
leisure activities, throughout their lifetime, and the relationship between these behaviors and gold-standard 
neuropsychological-neurophysiological markers of cognitive health, to understand presentation and 
mechanisms of individual adaptation to the environment through life. Neuropsychological measures of working 
memory and executive functions will be used to assess cognitive flexibility, while graph theoretical metrics of 
functional connectivity (FC) will be used to assess neurophysiological efficiency. Together, these components 
will give us a measure of neurocognitive adaptation, which is likely to clarify mechanisms of AD resilience. We 
will further investigate the role of AD risk factors and early pathology (amyloid, inflammation) in moderating 
effects of adaptive behavior on outcomes. Furthermore, as women show different structural and functional 
reserve characteristics, we will include sex as a factor when examining individual dynamic adaptation to the 
environment. The objective of this proposal is to investigate multiple domains (cognitive, physical, creative, and 
social) in 7-time windows from childhood (0-10 years old) to old age (+ 65 years old), exploring individual 
adaptation to the environment and its potential protective factors against neurodegeneration. Testing 
convergent validity of the dNA against gold-standard neuropsychological tests and fMRI measures of executive 
function in aging is an important innovation, and lays a foundation for implementing the dNA in at-risk and AD 
populations. The rationale for this project is that the concept of reserve is mostly static, based on unmodifiable 
variables (IQ and formal education), and poorly suited for understanding the role of time in this protective role. 
From our perspective, environment and learning change through the lifetime dynamically, as does individual 
subjective adaptation to environment. Specific Aim 1 will determine association of adaptation profiles with 
education and gold standard measures of cognitive flexibility, such as working memory, problem solving, setshifting, 
and inhibition in cognitively Healthy Controls (HCs). Our hypothesis is that greater maintenance in 
activities through lifetime will relate to higher education and better cognitive flexibility and peripheral 
inflammation will moderate this effect. Specific Aim 2 will establish association of adaptation profiles and gold 
standard measures of neurophysiological efficiency through fMRI (FC) and graph theoretical metrics during 
resting state. Our hypothesis is that greater maintenance in activities through lifetime will relate to better 
segregation of the Default ...

## Key facts

- **NIH application ID:** 11046491
- **Project number:** 5P20GM109025-09
- **Recipient organization:** CLEVELAND CLINIC FOUNDATION
- **Principal Investigator:** FILIPPO CIERI
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,500
- **Award type:** 5
- **Project period:** 2015-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11046491

## Citation

> US National Institutes of Health, RePORTER application 11046491, Beyond Reserve: Dynamic Neurocognitive Adaptation (5P20GM109025-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11046491. Licensed CC0.

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